Dendritic cells Flashcards
Functions of dendritic cells (3)
Present antigens to T-cells
Dendritic cells are the only cells that can activate naïve T-cells in vitro and in vivo
Dendritic cells capture antigens to present to T-cells
Describe dendritic maturation (5)
Immature DC continuously sample environments until there is damage
Capture the antigen
Go through maturation
Migrate to lymphoid organs
Mature DC switch on antigen presentation and present the antigen to T cells
Features of immature DC (3)
Found in the periphery e.g. skin and mucosa
Efficient antigen capture/uptake
Inefficient antigen presentation
Features of mature DC (2)
Inefficient antigen capture/uptake
Efficient antigen presentation/co-stimulation
Describe capture and uptake of antigens by DC (4)
Sample environment and take up molecules using complementary endocytic pathways:
Macropinocytosis
Receptor mediated endocytosis
Phagocytosis
Describe macropinocytosis (4)
Formation of large vesicles from the plasma membrane
Requires formation ruffles on the surface of the dendritic cell
Constitutive in immature dendritic cells
Enables the nonspecific uptake of large amounts of surrounding fluid and hence antigens in the fluid phase
What are the different receptors expressed by dendritic cells that are used to capture molecules? (10)
C-type lectins: mannose receptor and DEC205 recognize glycosylated proteins
Fc receptors: FcgammaRI and FcRI bind to Fc portion of antibodies and internalise immune complexes
Scavenger receptors: CD36 binds to apoptopic bodies
Receptors for heat shock proteins (HSP): bind Hsc70 and gp96 from tumour cells or infected cells and mediate uptake of HSP-peptide complexes
Receptors may function in both receptor mediated endocytosis and in phagocytosis
What do dendritic cells phagocytose? (3)
Almost any bacterium including Gram+ cocci, Gram + bacilli, mycobacteria
Yeast cells and fungal hyphae
Apoptopic and necrotic bodies
Dendritic cell will only maturation when? (2)
Until they are indicated there is tissue damage/infection
How do DCs mature? (4)
Through Toll like receptors which detect direct signals
Indirect signals: molecules secretion is triggered by pathogens or responses to tissue damage
How is macropinocytosis increased immediately after stimulation? (1)
Through TLR activation
Describe the process of migration of dendritic cells (3)
DC cell stimulated by infection
Move to lymphatic vessels to lymph nodes
Interact with T cells in the lymph nodes
What are the receptors involved in the migration of dendritic cells (10)
Langerhans cells interact with keratinocytes via E- cadherin, expression E-cadherin is reduced upon maturation
Chemokine receptor 7 (CCR7) is expression increased upon maturation- enables homing to lymph nodes
CCR7 has two chemokine ligands
– CCL21-expressed by endothelial cells of lymphatic vessels
– CCL19- expressed by stromal cells in the T cell zone of
lymph nodes
What are chemokines? (1)
Define where cells migrate to
(cells follow where there is more/less chemokine)
How is antigen presentation by dendritic cells regulated? (1)
Antigen presentation by dendritic cells is regulated by maturation
Antigen presentation by dendritic cells (2)
Present antigens to and activate naive CD4 (via MHC class II) and CD8 (via MHC class I) T-cells
Describe the MHC class 2 pathway of antigen presentation (6)
Capture of antigen through endocytic pathway
Antigen delivered to MIIC compartment (dendritic endosome)
MHC class 2 molecule have an association with a molecule known as the invariant chain
Variant chain binds to MHC class 2 molecule and blocks peptide binding groove and signals which target the MHC class 2 compartment
Invariant chain chopped up by proteases (present in the compartment) which reveals peptide binding site so interaction with antigen can occur
Proteolysis of antigens into short peptides which binds to MHC class 2 molecules which display these on the cell surface and this is recognised by receptors
Why is antigen presentation switched off in immature dendritic cells? (3)
Low activity vacuolar proton pump -> high endosomal/lysosomal pH - acidification of MIIC compartment cannot occur (enzymes cannot work)
High levels cystatin C prevents cleavage of Invariant chain by cathepsin S
Cell surface MHC class II rapidly endocytosed
Why is antigen presentation switched on in mature dendritic cells? (4)
High activity vacuolar proton pump -> low endosomal/lysosomal pH
Low levels cystatin C
Limited endocytosis of cell surface MHC class II
Transient increase in MHC class II synthesis upon maturation
Describe MHC class I pathway (6)
Antigens processed by proteasome into short peptides
Peptides translocated into endoplasmic reticulum where MHC class 1 molecule synthesised
Assessmble in ER
Bind to antigenic peptide
Traffic to cell surface and display so that they can be recognised by CD8 T cells
What is MHC class 1 pathway essential for? (2)
Monitoring cells for viral infections - which is why not switched off in immature dendritic cells
Regulation of MHC class I pathway in
dendritic cells (4)
Immature dendritic cells - Moderate expression MHC class I molecules (because they need to monitor cells for infections)
Mature dendritic cells - High level expression MHC class I molecules
Adaptation of MHC class 1 pathway that allows them to present exogenous antigens (4)
Dendritic cells can ‘break the rules’ and present exogenous (from outside the cell) antigens on MHC class I molecules to T-cells
This process is known as cross presentation and is essentially unique to dendritic cells
Cross presentation is important for the initiation of adaptive immunity
It is important because NOT all infectious agents infects dendritic cells, yet dendritic cells are required to activate naïve CD8+ T-cells
What are MHC class 2/class 1 involved in? (2(
class 2 - exogenous/extracellular antigen presentation
class 1 - endogenous/intracellular antigen presentation
Co-stimulation (4)
Secondary mode of activation that synergises with T cells signalling pathway to lead to activation of dendritic cell
Immature - low expression of costimulatory molecule
Mature - high expression of costimulatory molecule
Recognised by CD28 on T cell surface which transdues a costimualtory signal that leads to activation of T cell
Absence of costimulation - will not lead to activation of T cell by dendritic cell
